Significance of Stem Cell Marker Lgr5 Expression in Colorectal Carcinogenesis

Background: Lgr5 (Leucine rich repeat containing G-protein-coupled receptors) also known as G-protein-coupled receptor (Gpr-49). It belongs to the large, G-protein-coupled, 7-transmembrane (7TM) family of proteins. In order to determine whether Lgr5 is a potential marker of cancer stem cells, we investigated Lgr5 expression in normal colorectal mucosa, adenoma and carcinoma and compared the results with the clinicopathological data and prognosis. Methods: This is a retrospective study carried upon 40 Egyptian patients with different types of colorectal lesions, 6 cases of adenoma and 43 carcinoma (20 cases were cribriform adenocarcinoma, 6 signet ring carcinoma and 8 mucoid carcinoma). Six cases were taken as control from adjacent normal mucosa in patients with intestinal infarction. Lgr5 expression was evaluated by immunohistochemistry in the collected colorectal lesions. Results: Lgr5 was detected as cytoplasmic brown granules with different expression patterns in normal colonic mucosa, adenoma and carcinoma. Lgr5 expression was significantly higher in carcinoma than in adenoma (p 0.05). Statistical analysis revealed a significant increase in Lgr5 expression with progression from normal colon towards carcinoma (p 0.01). A significant statistical correlation was also found between Lgr5 expression and stage of colorectal carcinoma including depth of tumor invasion, lymph node metastasis and distant metastasis (p 0.05). Conclusions: Lgr5 may play an important role in colorectal tumorigenesis and invasion, and may be potential therapeutic target for the treatment of patients with colorectal cancer. It may also be considered as a potential marker for colorectal cancer stem cells (CSCs).